Amine derivatives, processes for preparing the same and fungicides containing the same

ABSTRACT

Amine derivatives having the general formula (I): ##STR1## wherein X is selected from the group consisting of ##STR2## wherein Q is oxygen, sulfur or nitrogen atom, and ##STR3## wherein Q is as above; Y is selected from the group consisting of ##STR4## R 1  is hydrogen atom or an alkyl group; R 2  is hydrogen atom or an alkyl group; R 3  is hydrogen atom, a halogen atom or an alkyl group; R 4  hydrogen atom, an alkyl group, a cycloalkyl group, a halogenated alkyl group or a halogen atom; R 5  is hydrogen atom, an alkyl group, an alkoxy group, a halogen atom, nitro group or hydroxy group; R 5  is attached to an arbitrary position of X, and R 3  or R 4  is attached to an arbitrary position of Y. 
     The amine derivatives (I) are useful as fungicides.

This application is a division of application Ser. No. 07/720,327, filedJun. 25, 1991, which application is a division of Ser. No. 07/479,894,now U.S. Pat. No. 5,106,866, filed Feb. 14, 1990, which application is adivision of Ser. No. 07/283,055, now U.S. Pat. No. 5,021,458, filed Dec.7, 1988, which application is a continuation of Ser. No. 07/073,329,filed Jul. 13, 1987, now abandoned, which application is a continuationof Ser. No. 06/740,596, filed Jun. 3, 1985, and now abandoned.

BACKGROUND OF THE INVENTION

The present invention relates to novel amine derivatives having thegeneral formula (I): ##STR5## wherein X is selected from the groupconsisting of ##STR6## wherein Q is oxygen, sulfur or nitrogen atom, and##STR7## wherein Q is as above; Y is selected from the group consistingof ##STR8## R¹ is hydrogen atom or a linear or branched alkyl grouphaving 1 to 6 carbon atoms, preferably having 1 to 4 carbon atoms; R² ishydrogen atom or linear or branched alkyl group having 1 to 6 carbonatoms, preferably having 1 to 4 carbon atoms; R³ is hydrogen atom, ahalogen atom such as fluorine, chlorine, bromine and iodine, or a linearor branched alkyl group having 1 to 6 carbon atoms, preferably having 1to 4 .carbon atoms; R⁴ is hydrogen atom, a linear or branched alkylgroup having 1 to 10 carbon atoms, preferably having 1 to 7 carbonatoms, cycloalkyl group having 3 to 7 carbon atoms, preferably having 5to 6 carbon atoms, halogenated alkyl group such as trifluoro methylgroup, or a halogen atom such as fluorine, chlorine, bromine and iodine;R⁵ is hydrogen atom, a linear or branched alkyl group having 1 to 6carbon atoms, preferably having 1 to 4 carbon atoms, a linear orbranched alkoxy group having 1 to 6 carbon atoms, preferably having 1 to4 carbon atoms, a halogen atom such as fluorine, chlorine, bromine andiodine, nitro group or hydroxy group; R⁵ is attached to an arbitraryposition of X, and R³ or R⁴ is attached to an arbitrary position of Y,processes for preparing the same and fungicides containing the same asan effective component.

The acid addition salts of said amine derivatives having general formula(I) are, for instance, hydrochloride, hydrobromide, sulfate, nitrate,acetate, oxalate, tartrate, benzenesulfate, methanesulfate and the like,which are pharmacologically acceptable.

The compounds according to the present invention can be prepared, forinstance, by the process (a) which comprises reacting the compoundhaving the general formula (II): ##STR9## wherein R¹, R⁵ and X are asabove, A is an eliminating group or R² --NH-- wherein R² is as above,with the compound having the general formula (III): ##STR10## whereinR³, R⁴ and Y are as above, A is an eliminating group or R² --NH--,wherein R² is as above, and A is different from that of formula (II) orthe process (b) which comprises reducing the compound having the generalformula (IV): ##STR11## wherein R³, R⁴, R⁵, X and Y are as above, W is##STR12## wherein R¹ and R² are as above, and by collecting the obtainedproduct from the process (a) or the process (b) in the form of a freebase or an acid addition salt.

The above-mentioned processes (a) and (b) can be carried out in theconventional manner.

The process (a) can be carried out in the reaction solvent of aromatichydrocarbon such as benzene and toluene, ether such as diethyl ether anddioxane, or carboxylic acid alkyl amide such as dimethylformamide at areaction temperature ranging from room temperature to a boiling point ofthe solvent, preferably from room temperature to 60° C. Examples ofeliminating group A are a halogen atom such as chlorine and bromine,organic sulfonyloxy group having 1 to 10 carbon atoms such as tosyloxyand mesyloxy. The reaction is advantageously carried out in the presenceof reagent binding with acid, i.e. hydroxide of alkali metal or alkalineearth metal, or carbonate of alkali metal or alkaline earth metal suchas sodium carbonate and potassium carbonate.

The process (b) can be carried out in an inactive solvent of ether suchas diethyl ether, tetrahydrofuran and dioxane at room temperature or areaction temperature ranging from room temperature to a boiling point ofthe solvent, using lithium aluminum hydride as a reducing agent.

The reaction to convert the compound of the present invention having thegeneral formula (I) from its free base into its acid addition salt, orfrom its acid addition salt into its free base, can be carried out inthe conventional manner.

The compounds having the general formula (II), (III) or (IV) which arethe starting materials and used for preparing the compound of thepresent invention having the general formula (I) can be produced easilyin the conventional manner whether or not they are known or novelcompounds. Examples of preparing them are as follows: ##STR13## whereinR¹, R², R³, R⁴, R⁵, X and Y are as above.

The reaction may be carried out under such conditions as usuallyemployed in such reaction and various intermediates can be subjected tofurther reaction without isolation. In case that isolation is necessary,it can be carried out by the conventional process.

The compounds of the present invention show an excellent antifungalactivity. They show an antifungal activity at the concentration of 0.003to 100 μg/ml in vitro especially against such fungi as Trichophytonmentagrophytes, Trichophyton interdigitale, Trichophyton rubrum,Microsporum canis, Microsporum gypseum, Epidermophyton floccosum,Cryptococcuss neoformans, Sporothrix schenekii, Aspergillus fumigatusand Candida albicans. In vivo test of dermatomycosis model employingguinea pig (see Sumio Sakai: Shinkin To Shinkinsho, vol. 1, page 252,1960) also ascertained that the compounds of the present invention havean excellent antifungal activity.

The compounds of the present invention can provide fungicides in theform of liquid preparation, ointment, cream and the like. Though anamount of an effective component may vary depending on species of fungi,a degree of disease, a kind of the compound employed, dosage form, andthe like, generally the compounds of the present invention can providefungicides at a concentration of 0.01 to 5%.

The present invention is further explained by the following ReferenceExamples, Examples, Preparation Examples and Test Examples. However, itis to be understood that the present invention is not limited to theseExamples and various changes and modifications may be made withoutdeparting from the spirit of the present invention.

The following NMR spectrum is shown in value measured in CDCl₃ employingTMS as standards.

Melting points in each Example are those of hydrochloride of thecompound and NMR spectrum are those of freebase of the compound.

REFERENCE EXAMPLE 1 [Preparation of 4-iodo-1-chloromethylnaphthalene ]

A mixture of 17.8 g of 1-iodo-naphthalene, 4.4 g of paraformaldehyde,10.4 ml of acetic acid, 14.6 ml of concentrated hydrochloric acid and6.6 ml of phosphoric acid was stirred at 80° to 85° C. and theretoanother 20 ml of concentrated hydrochloric acid was added with stirring8 times at intervals of 1 hour. The reaction mixture was poured intowater and was extracted with benzene. After distilling away benzene,18.5 g of 4-iodo-1-chloromethylnaphthalene was obtained.

Nuclear magnetic resonance spectrum δ (CDCl₃):

8.08 to 6.86 (m, 6H) and 4.78 (s, 2H)

The following compound was also prepared by the same procedures.

4-Bromo-1-chloromethylnaphthalene

Melting point: 82° to 83.5° C.

Nuclear magnetic resonance spectrum δ (CDCl₃):

8.33 to 7.15 (m, 6H) and 4.86 (s, 2H)

REFERENCE EXAMPLE 2 [Preparation of N-methyl-4-tert-butylbenzylamine]

A mixture of 178 g of 4-tert-Butyl benzoic acid and 360 g of thionylchloride was stirred at 50° C. for 5 hours. After distilling away anexcess of thionyl chloride under reduced pressure, the resultant wasadded dropwise to 300 ml of 40% aqueous solution of methylamine and theresultant mixture was stirred for 3 hours. Acidification withhydrochloric acid precipitated 171 g of N-methyl-4-tert-butyl benzamide(melting point: 99° to 100° C.).

To a mixture of 30.4 g of lithium aluminum hydride and 1 l of anhydrousdiethyl ether was added the obtained amide and the reaction mixture wasrefluxed for 6 hours. After cooling, an excess of lithium aluminumhydride was decomposed by adding dropwise of water and the ether layerwas separated. The ether solution was washed with water and dried overanhydrous solution sulfate. After distilling away ether, colourlessliquid of N-methyl-4-tert-butylbenzylamine (boiling point: 93 to 95°C./6 mmHg) was obtained by distillation under reduced pressure.

Nuclear magnetic resonance spectrum δ (CDCl₃):

7.26 (s, 4H), 3.68 (s, 2H), 2.42 (s, 3H) and 1.29 (s, 9H)

Melting point of hydrochloride: 208.5° to 209.5° C.

REFERENCE EXAMPLE 3 [Preparation of N-propyl-1-naphthylmethylamine]

To 116 g of propylamine was added dropwise 25 g of 1-naphthoyl chlorideand the resultant mixture was stirred for 3 hours. Then the crystalformed by acidification with hydrochloric acid was filtrated and waswashed with water. Obtained 26.8 g of N-propyl-1-naphthamide was addedto a mixture of 14.1 g of lithium aluminum hydride and 300 ml ofanhydrous diethyl ether and the reaction mixture was refluxed for 11hours. After cooling, an excess of lithium aluminum hydride wasdecomposed by adding dropwise of water and the ether layer wasseparated. After distilling away ether, 16.6 g ofN-propyl-1-nahthylmethylamine (boiling point: 133° to 134° C./1.5 mmHg)was obtained as colourless liquid by distillation under reducedpressure.

Nuclear magnetic resonance spectrum δ (CDCl₃):

8.2 to 7.2 (m, 7H), 4.20 (s, 2H), 2.69

(t, J=7 Hz, 2H), 1.86 to 1.15 (m, 2H) and

0.90 (t, J=7 Hz, 3H)

The following .compounds were also prepared by the same procedures.

N-Methyl-1-naphthylmethylamine N-Ethyl-1-naphthylmethylamineN-Butyl-1-naphthylmethylamine REFERENCE EXAMPLE 4 [Preparation ofN-methyl-N-(1-naphthylmethyl)-4-isopropyl benzamide]

A mixture of 0.99 g of 4-isopropyl benzoic acid and 3.6 g of thionylchloride was stirred at 50° C. for 4 hours and then an excess of thionylchloride was removed under reduced pressure. Obtained acid chloride wasdissolved into 5 ml of anhydrous benzene and the solution was addeddropwise to mixture of 1.03 g of N-methyl-1-naphthylmethylamine, 2 ml oftriethylamine and 15 ml of anhydrous benzene and the resultant wasstirred for 3 hours. The mixture was then poured into water, extractedwith benzene and washed successively with 5% aqueous solution ofhydrochloric acid, 3% aqueous solution of sodium bicarbonate and water.After distilling away benzene, viscousN-methyl-N-(1-naphthylmethyl)-4-isopropylbenzamide was obtained.

Nuclear magnetic resonance spectrum δ (CCl₄, TMS standard):

8.0 to 7.0 (m, 11H), 5.03 (s, 2H), 2.80 (s, 3H),

3.1 to 2.6 (m, 1H) and 1.18 (s, J=7 Hz, 6H)

The following compounds were also prepared by the same procedures.

N-Methyl-N-(1-naphthylmethyl)-4-ethylbenzamide Nuclear magneticresonance spectrum δ (CCl₄, TMS standard):

8.0 to 6.95 (m, 11H), 5.07 (s, 2H), 2.78 (s, 3H),

2.75 (q, J=7.6 Hz, 2H) and 1.15 (t, J=7.6 Hz, 2H)

N-Methyl-N- (1-naphthylmethyl)-4-butylbenzamide Nuclear magneticresonance spectrum δ (CCl₄, TMS standard):

8.0 to 6.9 (m, 11H), 5.02 (s, 2H), 2.79 (s, 3H),

2.79 (s, 3H), 2.54 (t, J=7 Hz, 2H), 1.7 to 1.15

(m, 4H) and 0.88 (t, J=7 Hz, 3H)

N-Methyl-N-(l-ha phthylmethyl)-3,4-dimethylbenzamide Nuclear magneticresonance spectrum δ (CCl₄, TMS standard):

8.0 to 6.8 (m, 10H), 4.99 (s, 2H), 2.76 (s, 3H) and 2.13 (s, 6H)

N-Methyl-N-(1-naphthylmethyl)-3,5-dimethylbenzamide

Nuclear magnetic resonance spectrum δ (CCl₁ TMS standard):

8.0 to 6.8 (m, 10H), 5.00 (s, 2H), 2.72 (s, 3H) and 2.15 (s, 6H)

N-Methyl-N-(1-naphthylmethyl) -4- iodobenzamide

Melting point: 136.5° to 138.5° C.

Nuclear magnetic resonance spectrum δ (CCl₄, TMS standard):

8.0 to 7.01 (m, 11H), 5.03 (s, 2H) and 2.80 (s, 3H)

REFERENCE EXAMPLE 5 [Preparation ofN-(4-tert-buthylbenzyl)-N-methyl-2-ethoxycarboxy-1-naphthamide ]

Into an aqueous solution of sodium hydroxide (3.63 g of sodium hydroxideand 71.5 ml of water) was dissolved 7.52 g of 2-hydroxy-1-naphthoic acidand thereto 9.59 g of ethyl chloroformate was added dropwise at cooling.After the mixture was stirred at room temperature for 1 hour, it waspoured into water, extracted with benzene, washed with water and driedover anhydrous sodium sulfate. Sodium sulfate was removed and then 5.24g of thionyl chloride was added. The reaction was carried out at 40° C.for 3 hours and the obtained acid chloride was added dropwise to amixture of 7.08 g of N-methyl-4-tert-benzylamine and 8 g of pyridine andthen stirred for 3 hours. The reaction mixture was poured into water,extracted with benzene, and the benzene solution was washed successivelywith 3% aqueous solution of hydrochloric acid, subsequently with water,and dried over anhydrous sodium sulfate. After distilling away benzene,6.6 g of oilyN-(4-tert-butylbenzyl)-methyl-2-ethoxycarboxy-1-naphthamide wasobtained.

EXAMPLE 1

A mixture of 1.94 g of 1-chloromethylnaphthalene, 1.77 g ofN-methyl-4-tert-butylbenzylamine, 1.17 g of sodium carbonate and 10 mlof dimethylformamide was stirred for 14 hours at 50° C. The reactionmixture was poured into water and extracted with benzene, and thebenzene solution was washed with water. After distilling away benzene,1.5 ml of concentrated hydrochloric acid was added, an excess ofconcentrated hydrochloric acid was removed under reduced pressure, asmall amount of acetone was added and formed white crystal (2.75 g) wasfiltrated. White plate crystal ofN-(4-tert-butylbenzyl)-N-methyl-1-naphthylmethylamine hydrochloride wasobtained by recrystallization from acetone/ethanol.

Melting point: 211° to 213° C.

Nuclear magnetic resonance spectrum δ:

8.3 to 7.3 (m, 11H), 3.91 (s, 2H), 3.56 (s, 2H),

2.19 (s, 3H) and 1.33 (s, 9H)

Mass spectrum (m/e):

317 (M⁺), 190, 176, 170, 147 and 141 (base)

EXAMPLE 4

N-4-tert-Butylbenzyl-N-methyl-4-fluoro-1-naphthamide (2.0 g) wasobtained by the reaction of 1.23 g of 1-Chloromethyl-4-fluoronaphthaleneand 1.15 g of N-Methyl-4-tert-butylbenzylamine.

EXAMPLE 9

N-4-tert-Butylbenzyl-N-methyl-1-(1-naphthyl)-ethylamine (1.33 g) wasobtained by the reaction of 1.20 g of 1-(1-Chloroethyl)naphthalene and1.15 g of N-Methyl-4-tert-butylbenzyl amine.

EXAMPLE 12

N-Methyl-N-4- tert-pentylbenzyl-1-naphthyl-methylamine (1.65 g) wasobtained by the reaction of 1.11 g of 1-Chloromethylnaphthalene and 1.15g of N-Methyl-4-tert-pentylbenzylamine.

EXAMPLE 22

N-4-Isopropylbenzyl-N-methyl-1-naphthyl-methylamine (1.47 g) wasobtained by the reaction of 1.11 g of 1-Chloromethylnaphthalene and 0.98g of N-Methyl-4-isopropylbenzylamine.

EXAMPLE 29

N-4-tert-Butylbenzyl-N-methyl-3-benzo[b ]-thienylmethylamine (1.4 g) wasobtained by the reaction of 0.89 g of 3-Chloromethylbenzo[b]thiopheneand 0.91 g of N-Methyl-4-tert-butylbenzylamine.

EXAMPLES 2 to 71

The procedures of Example 1 were repeated to give hydrochlorides ofvarious amine derivatives. Melting points of each compounds are shown inTable 1.

                                      TABLE 1                                     __________________________________________________________________________     ##STR14##                                                                     No.                                                                              XR.sup.5       R.sup.1                                                                          R.sup.2                                                                          ##STR15##     Melting point (°C.)             __________________________________________________________________________     1                                                                                ##STR16##     H  CH.sub.3                                                                          ##STR17##    211 to 213                               2                                                                                ##STR18##     "  "  "             218 to 220                               3                                                                                ##STR19##     "  "  "             231 to 233                               4                                                                                ##STR20##     "  "  "             237 to 239                               5                                                                                ##STR21##     "  "  "             236 to 238                               6                                                                                ##STR22##     "  "  "             240 to 242                               7                                                                                ##STR23##     H  CH.sub.3                                                                          ##STR24##    225 to 227                               8                                                                                ##STR25##     "  "  "             223 to 225                               9                                                                                ##STR26##     CH.sub.3                                                                         "  "             222 to 224                              10                                                                                ##STR27##     H  "  "             228.5 to 230.5                          11                                                                                ##STR28##     "  "  "             196 to 198                              12                                                                                ##STR29##     "  "                                                                                 ##STR30##    191 to 193                              13 "              "  "                                                                                 ##STR31##    213 to 214                              14                                                                                ##STR32##     H  CH.sub.3                                                                          ##STR33##    197 to 199                              15 "              "  "                                                                                 ##STR34##    192 to 194                              16 "              "  "                                                                                 ##STR35##    205 to 207                              17 "              "  "                                                                                 ##STR36##    211 to 212.5                            18 "              "  C.sub.2 H.sub.5                                                                   ##STR37##    190 to 195                              19 "              "  C.sub.3 H.sub.7                                                                  "             174 to 176.5                            20 "              "  C.sub.4 H.sub.9                                                                  "             165 to 170                              21                                                                                ##STR38##     H  CH.sub.3                                                                          ##STR39##    211 to 213                              22 "              "  "                                                                                 ##STR40##    195.5 to 197                            23 "              "  "                                                                                 ##STR41##    202 to 203.5                            24 "              "  "                                                                                 ##STR42##    190 to 191                              25 "              "  "                                                                                 ##STR43##    197.5 to 199                            26 "              "  "                                                                                 ##STR44##    188 to 189                              27 "              "  "                                                                                 ##STR45##    215 to 217                              28                                                                                ##STR46##     H  CH.sub.3                                                                          ##STR47##    181 to 183                              29                                                                                ##STR48##     "  "  "             216 to 217.5                            30 "              "  C.sub.2 H.sub.5                                                                  "             173 to 175                              31 "              "  CH.sub.3                                                                          ##STR49##    223 to 224                              32 "              "  "                                                                                 ##STR50##    237 to 238                              33                                                                                ##STR51##     "  "                                                                                 ##STR52##    219 to 221                              34                                                                                ##STR53##     "  "  "             219 to 221                              35                                                                                ##STR54##     "  "                                                                                 ##STR55##                                            36                                                                                ##STR56##     "  "  "                                                     37                                                                                ##STR57##     "  "  "             220 to 221.5                            38                                                                                ##STR58##     "  "  "             210 to 212 (dec)                        39                                                                                ##STR59##     "  "  "             189.5 to 190.5                          40                                                                                ##STR60##     "  "  "             237 to 238                              41                                                                                ##STR61##     "  "  "             232.5 to 233 (dec)                      42                                                                                ##STR62##     H  CH.sub.3                                                                          ##STR63##    237 to 239                              43 "              "  "                                                                                 ##STR64##    243 to 243.5                            44                                                                                ##STR65##     "  "                                                                                 ##STR66##    233 to 234                              45 "              "  "                                                                                 ##STR67##    247 to 249                              46                                                                                ##STR68##     "  "                                                                                 ##STR69##    228 to 228.5                            47 "              "  "                                                                                 ##STR70##    235.5 to 236.5                          48                                                                                ##STR71##     H  CH.sub.3                                                                          ##STR72##    219 to 220                              49                                                                                ##STR73##     "  "                                                                                 ##STR74##    238 to 239                              50                                                                                ##STR75##     "  "  "             233 to 236                              51                                                                                ##STR76##     CH.sub.3                                                                         "  "             215 to 217                              52 "              H  "                                                                                 ##STR77##    192 to 194                              53 "              "  "                                                                                 ##STR78##    126 to 128 (dec)                        54                                                                                ##STR79##     H  CH.sub.3                                                                          ##STR80##    197 to 200                              55 "              "  C.sub.2 H.sub.5                                                                   ##STR81##    194 to 196                              56 "              "  "                                                                                 ##STR82##    174 to 179                              57 "              "  C.sub.3 H.sub.7                                                                   ##STR83##    163 to 169                              58 "              "  "                                                                                 ##STR84##    183 to 186                              59 "              "  C.sub.4 H.sub.9                                                                   ##STR85##    173 to 176                              60 "              "  "                                                                                 ##STR86##                                            61                                                                                ##STR87##     H  CH.sub.3                                                                          ##STR88##                                            62 "              "  C.sub.2 H.sub.5                                                                   ##STR89##    214 to 215                              63 "              "  "                                                                                 ##STR90##    194 to 195                              64 "              "  C.sub.3 H.sub.7                                                                   ##STR91##    193 to 194                              65 "              "  "                                                                                 ##STR92##    206 to 208.5                            66 "              "  C.sub.4 H.sub.9                                                                   ##STR93##    156 to 158                              67 "              "  "                                                                                 ##STR94##    177 to 179                              68                                                                                ##STR95##     H  CH.sub.3                                                                          ##STR96##    102 to 103 (base)                       69 "              "  "                                                                                 ##STR97##    199 to 201.5                            70 "              "  H                                                                                 ##STR98##    203 to 208                              71                                                                                ##STR99##     "  CH.sub.3                                                                         "                                                     __________________________________________________________________________

The followings are NMR and MS (m/e) data of each compound of Examples 2to 71.

EXAMPLE 2

Nuclear magnetic resonance spectrum δ:

8.35 to 7.23 (m, 10H), 3.97 (s, 2H), 3.54 (s, 2H),

2.57 (s, 3H), 2.17 (s, 3H) and 1.28 (s, 9H)

Mass spectrum (m/e):

331 (M⁺), 176, 152 (base)and 147

EXAMPLE 3

Nuclear magnetic resonance spectrum δ:

8.4 to 7.3 (m, 10H), 3.88 (s, 2H), 3.53 (s, 2H),

2.63 (s, 3H), 2.13 (s, 3H)and 1.28 (s, 9H)

Mass spectrum (m/e):

331 (M³⁰), 184,176, 152 (base) and 147

EXAMPLE 4

Nuclear magnetic resonance spectrum δ:

8.3 to 6.8 (m, 10H), 3.84 (s, 2H), 3.52 (s, 2H),

2.18 (s, 3H)and 1.30 (s, 9H)

Mass spectrum (m/e):

335 (M³⁰), 188, 176, 154 (base)and 147

EXAMPLE 5

Nuclear magnetic resonance spectrum δ:

8.3 to 7.3 (m, 10H), 3.83 (s, 2H), 3.53 (s, 2H),

2.17 (s, 3H)and 1.30 (s, 9H)

Mass spectrum (m/e):

351 (M³⁰), 204,176, 175 (base) and 147

EXAMPLE 6

Nuclear magnetic resonance spectrum δ:

8.3 to 7.3 (m, 10H), 3.77 (s, 2H), 3.50 (s, 2H),

2.13 (s, 3H)and 1.29 (s, 9H)

Mass spectrum (m/e):

397 (M³⁰), 395 (M³⁰), 250, 248, 219, 201, 176 (base) and 147

EXAMPLE 7

Nuclear magnetic resonance spectrum δ:

8.3 to 7.1 (m, 10H), 3.82 (s, 2H), 3.52 (s, 2H),

2.17 (s, 3H) and 1.30 (s, 9H)

Mass spectrum (m/e):

443 (M³⁰), 296, 267, 217,176 (base) and 147

EXAMPLE 8

Nuclear magnetic resonance spectrum δ:

8.6 to 7.3 (m, 10H), 3.91 (s, 2H), 3.54 (s, 2H),

2.19 (s, 3H) and 1.29 (s, 9H)

Mass spectrum (m/e):

362 (M³⁰), 215, 186, 176 and 147 (base)

EXAMPLE 9

Nuclear magnetic resonance spectrum δ:

8.54 to 7.22 (m, 11H), 4.36 (q, J=6.6 Hz, 1H),

3.63 (d, J=13 Hz, 1H), 3.34 (d, J=13 Hz, 1H ),

2.19 (s, 3H), 1.53 (d, J=6.6 Hz, 2H ) and

1.28 (s, 9H)

Mass spectrum (m/e):

331 (M³⁰), 316, 204, 176 , 152 and 147 (base)

EXAMPLE 10

Nuclear magnetic resonance spectrum δ:

7.9 to 7.3 (m, 11H), 3.63 (s, 2H), 3.53 (s, 2H),

2.21 (s, 3H)and 1.31 (s, 9H)

Mass spectrum (m/e):

317 (M³⁰), 176 (base), 170, 147, 142 and 141

EXAMPLE 11

Nuclear magnetic resonance spectrum δ:

8.3 to 7.1 (m, 10H), 3.98 (s, 2H), 3.88 (s, 3H),

3.55 (s, 2H) 2.20 (s, 3H) and 1.28 (s, 9H)

Mass spectrum (m/e):

347 (M³⁰), 200, 176, 171 (base), 147 and 141

EXAMPLE 12

Nuclear magnetic resonance spectrum δ:

8.3 to 7.3 (m, 11H), 3.88 (s, 2H), 3.54 (s, 2H),

2.17 (s, 3H), 1.61 (q, J=7.3 Hz, 2H), 1.26 (s, 6H)

and 0.67 (t, J=7.3 Hz, 3H)

Mass spectrum (m/e):

331 (M³⁰), 190, 170, 155 and 141 (base)

EXAMPLE 13

Nuclear magnetic resonance spectrum δ:

8.3 to 7.1 (m, 11H), 3.90 (s, 2H),

2.33 (s, 3H) and 2.19 (s, 3H)

Mass spectrum (m/e):

275 (M³⁰), 170, 141 (base), 134 and 105

EXAMPLE 14

Nuclear magnetic resonance spectrum δ:

8.3 to 7.3 (m, 11H), 3.87 (s, 2H), 3.53 (s, 2H) and 2.16 (s, 3H)

Mass spectrum (m/e):

329 (M³⁰), 202, 188, 154, 142 and 141 (base)

EXAMPLE 15

Nuclear magnetic resonance spectrum δ:

8.3 to 7.0 (m, 11H), 3.87 (s, 2H), 3.53 (s, 2H),

2.29 (s, 3H) and 2.15 (s, 3H)

Mass spectrum (m/e):

275 (M³⁰), 170, 141 (base), 134 and 115

EXAMPLE 16

Nuclear magnetic resonance spectrum δ:

8.3 to 7.0 (m, 11H), 3.89 (s, 2H), 3.54 (s, 2H),

2.5 (m, 1H), 2.17 (s, 3H)and 2 to 1.1 (m, 10H)

Mass spectrum (m/e):

343 (M³⁰), 202, 173, 170 and 141 (base)

EXAMPLE 17

Nuclear magnetic resonance spectrum δ:

8.3 to 7.0 (m, 10H), 3.87 (s, 2H), 3.43 (s, 2H) and 2.15 (s, 3H)

Mass spectrum (m/e):

329 (M³⁰), 202, 188, 170, 142 and 141 (base)

EXAMPLE 18

Nuclear magnetic resonance spectrum δ:

8.3 to 7.2 (m, 11H), 3.97 (s, 2H), 3.54 (s, 2H),

2.56 (q, J=7 Hz, 2H), 1.24 (s, 9H) and 1.02

t, J=7 Hz, 3H)

Mass spectrum (m/e):

331 (M³⁰), 316, 190, 147 and 141 (base)

EXAMPLE 19

Nuclear magnetic resonance spectrum δ:

8.3 to 7.2 (m, 11H), 3.91 (s, 2H), 3.53 (s, 2H),

2.59 (t, J=7Hz, 2H), 1.74 to 1.47 (m, 2H),

1.25 (s, 9H) and 0.78 (t, J=7 Hz, 3H)

Mass spectrum (m/e):

345 (M³⁰), 316, 147 and 141 (base)

EXAMPLE 20

Nuclear magnetic resonance spectrum δ:

8.3 to 7.2 (m, 11H), 3.94 (s, 2H), 3.53 (s, 2H),

2.48 (t, J=7 Hz, 2H) and 1.24 (s, 9H)

Mass spectrum (m/e):

359 (M³⁰), 316, 147 and 141 (base)

EXAMPLE 21

Nuclear magnetic resonance spectrum δ:

8.3 to 7.06 (m, 11H), 3.89 (s, 2H), 3.47 (s, 2H) and 2.15 (s, 3H)

Mass spectrum (m/e):

341 (M⁺), 339 (M⁺), 200, 198, 171, 169 and 141 (base)

EXAMPLE 22

Nuclear magnetic resonance spectrum δ:

8.3 to 7.0 (m, 11H), 3.90 (s, 2H), 3.54 (s, 2H),

3.80 (q, J=7.4 Hz, 1H), 2.17 (s, 3H) and 1.22

(d, J=7.4 Hz, 6H)

Mass spectrum (m/e):

303 (M³⁰), 170, 155, 141 (base) and 133

EXAMPLE 23

Nuclear magnetic resonance spectrum δ:

8.3 to 7.0 (m, 11H), 3.88 (s, 2H), 3.54 (s, 2H),

2.59 (q, J=7 Hz, 2H), 2.16 (s, 3H) and 1.19

(t, J=7 Hz, 3H)

Mass spectrum (m/e):

289 (M³⁰), 170, 148, 141 (base) and 119

EXAMPLE 24

Nuclear magnetic resonance spectrum δ:

8.3 to 7.0 (m, 11H), 3.88 (s, 2H), 3.55 (s, 2H),

2.58 (t, J=7 Hz, 2H), 2.16 (s, 3H)and 1.9 to 1.2 (m, 4H )

Mass spectrum (m/e):

317 (M³⁰), 176, 147 and 141 (base)

EXAMPLE 25

Nuclear magnetic resonance spectrum δ:

8.3 to 7.05 (m, 10H), 4.86 (s, 2H), 4.51 (s, 2H),

2.22 (s, 6H) and 2.16 (s, 3H)

Mass spectrum (m/e):

289 (M³⁰), 170, 148, 141 (base) and 119

EXAMPLE 26

Nuclear magnetic resonance spectrum δ:

8.3 to 6.9 (m, 10H), 3.88 (s, 2H), 3.53 (s, 2H),

2.29 (s, 6H)and 2.19 (s, 3H)

Mass spectrum (m/e):

289 (M³⁰), 170, 148, 141 (base) and 119

EXAMPLE 27

Nuclear magnetic resonance spectrum δ:

8.3 to 6.89 (m, 11H), 3.83 (s, 2H), 3.39 (s, 2H) and 2.10 (s, 3H)

Mass spectrum (m/e):

387 (M³⁰), 260, 246, 217, 170 and 141

EXAMPLE 28

Nuclear magnetic resonance spectrum δ:

7.9 to 7.15 (m, 10H), 4.16 (s, 2H), 3.63 (s, 2H),

2.30 (s, 3H) and 1.31 (s, 9H)

Mass spectrum (m/e):

333 (M³⁰), 176 (base), 153, 147, 128 and 120

EXAMPLE 29

Nuclear magnetic resonance spectrum δ:

8.0 to 7.2 (m, 9H), 3.74 (s, 2H), 3.54 (s, 2H),

2.21 (s, H)and 1.30 (s, 9H)

Mass spectrum (m/e):

147 (base), 148, 176 and 232 (M⁺)

EXAMPLE 30

Nuclear magnetic resonance spectrum δ:

8.0 to 7.2 (m, 9H), 3.76 (s, 2H), 3.55 (s, 2H),

2.54 (t, J=7.2 Hz, 2H), 1.28 (s, 9H) and 1.07

(t, J=7.2 Hz, 3H)

Mass spectrum (m/e):

147 (base), 148, 190, 322 and 337 (M⁺)

EXAMPLE 31

Nuclear magnetic resonance spectrum δ:

8.2 to 7.1 (m, 12H), 3.90 (s, 2H), 3.73 (s, 2H) and 2.20 (s, 3H)

Mass spectrum (m/e):

141,147 (base), 148, 170, 176 and 317 (M⁺)

EXAMPLE 32

Nuclear magnetic resonance spectrum δ:

8.0 to 7.2 (m, 12H), 3.73 (s, 2H), 3.65 (s, 2H) and 2.20 (s, 3H)

Mass spectrum (m/e):

141, 142, 147 (base), 148, 170, 176 and 317 (M)

EXAMPLE 33

Nuclear magnetic resonance spectrum δ:

7.9 to 7.4 (m, 8H), 3.72 (s, 2H), 2.52 (s, 3H),

2.20 (s, 2H) and 1.29 (s, 9H)

Mass spectrum (m/e):

190 and 337 (M⁺)

161 (base), 162, 176, 190 and 337 (M⁺)

EXAMPLE 34

Nuclear magnetic resonance spectrum δ:

7.83 to 7.23 (m, 9H), 3.78 (s, 2H), 3.53 (s, 2H),

2.17 (s, 3H)and 1.32 (s, 9H)

Mass spectrum (m/e):

147 (base), 148, 176, 190 and 323 (M⁺)

EXAMPLE 37

Nuclear magnetic resonance spectrum δ:

7.64 (m, 8H), 3.73 (s, 2H), 3.57 (s, 2H), 2.15

(s, 3H)and 1.31 (s, 9H)

Mass spectrum (m/e):

147, 176 (base), 225, 227, 254, 256 401 (M⁺)

and 403 (M⁺)

EXAMPLE 38

Nuclear magnetic resonance spectrum δ:

7.28 to 7.12 (m, 7H), 3.47 (s, 4H), 2.88

(t, J=7 Hz, 4H), 2.17 (s, 3H), 2.02 (t, J=7 Hz, 2H)

and 1.30 (s, 9H)

Mass spectrum (m/e):

131 (base), 132, 147, 160, 176 and 307 (M⁺)

EXAMPLE 39

Nuclear magnetic resonance spectrum δ:

7.27 to 6.93 (m, 7H), 3.48, 3.45 (s, s, 4H),

2.95 to 2.62 (m, 4H), 2.13 (s, 3H), 1.88 to

1.67 (m, 4H)and 1.32 (s, 9H)

Mass spectrum (m/e):

129, 144 (base), 145, 147, 176, 178 and 321 (M⁺)

EXAMPLE 40

Nuclear magnetic resonance spectrum δ:

7.27 (s, 4H), 7.03 (s, 3H), 3.48, 3.45 (s, s, 4H),

2.9 to 2.6 (m, 4H), 2.16 (s, 3H), 1.88 to 1.67

(m, 4H ) and 1.29 (s, 9H )

Mass spectrum (m/e):

139, 140, 141, 174, 176 (base) and 321 (M⁺)

EXAMPLE 41

Nuclear magnetic resonance spectrum δ:

8.15 to 6.83 (m,13H), 3.91 (s,2H), 3.81 (s,2H)

and 2.19 (s,3H)

Mass spectrum (m/e):

137, 149 (base), 170, 188 and 327 (M⁺)

EXAMPLE 42

Nuclear magnetic resonance spectrum δ:

8.15 to 6.83 (m, 13H), 3.91 (s, 2H), 3.85 (s, 2H)

and 2.19 (s, 3H)

Mass spectrum (m/e):

147, 154 (base), 176, 188 and 335 (M⁺)

EXAMPLE 43

Nuclear magnetic resonance spectrum δ:

8.36 to 6.87 (m, 13H), 3.90 (s, 2H), 3.71 (s, 2H)

and 2.19 (s, 3H)

Mass spectrum (m/e):

137, 138, 149 (base), 170, 188 and 329 (M⁺)

EXAMPLE 44

Nuclear magnetic resonance spectrum δ:

8.3 to 7.1 (m, 13H), 3.94 (s, 2H), 3.87 (s, 2H) and 2.21 (s, 9H)

Mass spectrum (m/e):

137 (base), 138, 170, 175, 204 and 345 (M⁺)

EXAMPLE 45

Nuclear magnetic resonance spectrum δ:

8.35 to 7.2 (m, 13H), 3.84 (s, 2H), 3.66 (s, 2H) and 2.16 (s, 3H)

Mass spectrum (m/e):

137 (base), 138, 170, 175, 204 and 345 (M⁺)

EXAMPLE 46

Nuclear magnetic resonance spectrum δ:

8.32 to 7.11 (m, 13H), 3.92 (s, 2H), 3.83 (s, 2H) and 2.19 (s, 3H)

Mass spectrum (m/e):

137 (base), 138, 170, 219, 221, 248, 250, 389 and 391 (M⁺)

EXAMPLE 47

Nuclear magnetic resonance spectrum δ(in DMSO-d₆):

8.47 to 7.45 (m, 13H), 3.92 (s, 2H), 3.72 (s, 2H) and 2.16 (s, 3H)

Mass spectrum (m/e):

137 (base), 138, 170, 219, 221, 248, 250, 389 and 391 (M⁺)

EXAMPLE 48

Nuclear magnetic resonance spectrum δ:

8.2 to 7.1 (m, 13H), 3.90 (s, 4H), 2.61 (s, 3H) and 2.19 (s, 3H)

Mass spectrum (m/e):

137, 146 (base), 147, 170, 184 and 325 (M⁺)

EXAMPLE 49

Nuclear magnetic resonance spectrum δ:

8.44 to 7.3 (m, 13H), 3.95 (s, 2H), 3.74 (s, 2H),

2.66 (s, 3H) and 2.22 (s, 3H)

Mass spectrum (m/e):

137 (base), 138, 146 (base), 147, 170, 184 and 325 (M⁺)

EXAMPLE 50

Nuclear magnetic resonance spectrum δ:

8.57 to 7.23 (m, 13H), 3.85 (s, 2H), 3.66 (s, 2H) and 2.16 (s, 3H)

Mass spectrum (m/e):

137 (base), 138, 170, 186, 215 and 356 (M⁺)

EXAMPLE 51

Nuclear magnetic resonance spectrum δ:

8.55 to 7.3 (m, 14H), 4.40 (q, J=6.5 Hz, 1H),

3.70, 3.63 (s, s, 2H), 2.21 (s, 3H)and

1.59 (d, J=6.5 Hz, 3H)

Mass spectrum (m/e):

137 (base), 146, 162, 170, 184, 198, 310 and 325 (M⁺)

EXAMPLE 52

Nuclear magnetic resonance spectrum δ:

8.37 to 7.02 (m, 10H), 3.85 (s, 2H), 3.47 (s, 2H),

2.81 (t, J=7 Hz, 4H), 2.13 (s, 3H) and 2.01

(t, J=7 Hz, 2H)

Mass spectrum (m/e):

131, 137 (base), 150, 170 and 301 (M⁺)

EXAMPLE 53

Nuclear magnetic resonance spectrum δ:

8.0 to 6.8 (m, 10H), 3.73 (s, 2H), 3.36 (s, 2H),

2.9 to 2.5 (m, 4H), 2.07 (s, 3H) and 1.8 to 1.5

(s, 4H)

Mass spectrum (m/e):

129, 137, 139 (base), 172 and 315 (M⁺)

EXAMPLE 54

Nuclear magnetic resonance spectrum δ:

8.26 to 6.86 (m, 10H), 3.80 (s, 2H), 3.42 (s, 2H),

2.8 to 2.5 (m, 4H), 2.11 (s, 3H) and 1.9 to 1.6

(m, 4H )

Mass spectrum (m/e):

137 (base), 139, 170, 174 and 315 (M⁺)

EXAMPLE 55

Nuclear magnetic resonance spectrum δ:

8.09 to 6.94 (m, 10H), 3.91 (s, 2H), 3.54 (s, 2H),

2.9 to 2.5 (m, 4H), 2.51 (q, J=7 Hz, 2H), 1.9 to

1.6 (m, 4H) and 1.05 (t, J=7 Hz, 3H)

Mass spectrum (m/e):

137, 138 (base), 184, 186 and 329 (M⁺)

EXAMPLE 56

Nuclear magnetic resonance spectrum δ:

8.38 to 7.01 (m, 10H), 3.99 (s, 2H), 3.56 (s, 2H),

2.9 to 2.38 (m, 6H), 1.9 to 1.6 (m, 4H) and

1.07 (t, J=7 Hz, 3H)

Mass spectrum (m/e):

137 (base), 139, 184, 188, 314 and 329 (M⁺)

EXAMPLE 57

Nuclear magnetic resonance spectrum δ:

8.12 (m, 10H), 3.94 (s, 2H), 3.56 (s, 2H),

3.0 to 2.33 (m, 6H), 1.9 to 1.28 (m, 6H ) and

0.77 (t, J=7 Hz, 3H)

Mass spectrum (m/e):

137 (base), 139, 198, 200, 314 and 343

EXAMPLE 58

Nuclear magnetic resonance spectrum δ:

8.35 to 7.03 (m, 10H), 3.98 (s, 2H), 3.57 (s, 2H),

2.9 to 2.34 (m, 6H), 1.9 to 1.3 (m, 6H) and

0.78 (t, J=7 Hz, 3H)

Mass spectrum (m/e):

137 (base), 139, 314 and 343 (M⁺)

EXAMPLE 59

Nuclear magnetic resonance spectrum δ:

8.1 to 6.9 (m, 10H ), 3.92 (s, 2H), 3.55 (s, 2H),

2.9 to 3.33 (m, 6H), 1.9 to 1.0 (m, 8H ) and

0.76 (t, J=6 Hz, 3H)

Mass spectrum (m/e): 137 (base), 139, 212,214,314 and 357 (M⁺)

EXAMPLE 60

Nuclear magnetic resonance spectrum δ:

8.35 to 7.04 (m, 1 0H), 3.95 (s, -2H), 3.54 (s, 2H),

2.9 to 2.37 (m, 6H ), 1.9 to 1.0 (m, 8H ) and

0.79 (t, J=6 Hz, 3H)

Mass spectrum (m/e):

137 (base), 139, 314 and 357 (M⁺)

EXAMPLE 62

Nuclear magnetic resonance spectrum δ:

8.14 to 7.04 (m, 14H), 3.95 (s, 4H), 2.54

(q, J=7.5 Hz, 2H) and 1.07 (t, J=7.5 Hz, 3H)

Mass spectrum (m/e):

137 (base), 138, 184. 310 and 325 (M⁺)

EXAMPLE 63

Nuclear magnetic resonance spectrum δ:

8.37 to 7.15 (m, 14H), 3.90 (s, 2H), 3.60 (s, 2H),

2.49 (q, J=7 Hz, 2H) and 1.00 (t, J=7 Hz, 3H)

Mass spectrum (m/e):

1.37 (base), 138, 184, 310 and 325 (M⁺)

EXAMPLE 64

Nuclear magnetic resonance spectrum δ:

8.12 to 7.06 (m, 1 4H), 3.97 (s, 4H), 2.59 to

2.33 (m, 2H), 1.9 to 1.3 (m, 2H ) and 0.71

(t, J=7 Hz, 3H),

Mass spectrum (m/e):

137 (base), 310 and 339 (M⁺)

EXAMPLE 65

Nuclear magnetic resonance spectrum

8.36 to 7.2 (m, 14H), 3.98 (s, 2H), 3.68 (s, 2H),

2.50 (t, J=7 Hz, 2H), 1.7 to 1.1 (m, 2H ) and

0.75 (t, 3H)

Mass spectrum (m/e):

137 (base), 138, 198, 310 and 339 (M⁺)

EXAMPLE 66

Nuclear magnetic resonance spectrum δ:

8.11 to 7.0 (m, 14H), 3.93 (s, 4H), 2.46

(t, J=6.5 Hz, 2H), 1.6 to 0.9 (m, 4H ) and

0.69 (t, J=6 Hz, 3H)

Mass spectrum (m/e):

137 (base), 138, 212,310 and 353 (M⁺)

EXAMPLE 67

Nuclear magnetic resonance spectrum δ:

8.4 to 7.35 (m, 14H), 4.06 (s, 2H), 3.77 (s, 2H),

2.54 (t, J=7 Hz, 2H), 1.8 to 0.9 (m, 4H ) and

0.77 (t, J=6 Hz, 3H)

Mass spectrum (m/e):

137 (base), 138, 212, 310 and 353 (M⁺)

EXAMPLE 68

Nuclear magnetic resonance spectrum δ:

8.44 to 7.2 (m, 13H), 4.02 (s, 2H), 3.91 (s, 2H) and 2.28 (s, 3H)

Mass spectrum (m/e):

138 (base), 170 and 312 (M⁺)

EXAMPLE 69

Nuclear magnetic resonance spectrum δ:

8.4 to 6.7 (m, 9H), 3.95 (s, 2H), 3.76,(s, 2H),

2.25 (s, 3H) and 1.33 (s, 9H)

Mass spectrum (m/e):

137, 141 (base), 144, 182, 190 and 323 (M⁺)

EXAMPLE 70

Nuclear magnetic resonance spectrum δ:

8.13 to 7.28 (m, 9H), 4.11 (s, 2H), 3.83 (s, 2H),

1.74 (broad s, 1H)and 1.29 (s, 9H)

Mass spectrum (m/e):

137 (base), 138, 141,147, 151 and 303 (M⁺)

EXAMPLE 71

Nuclear magnetic resonance spectrum δ:

8.82 to 7.26 (m, 10H), 3.85 (s, 2H), 3.54 (s, 2H),

2.17 (s, 3H)and 1.27 (s, 9H)

Mass spectrum (m/e):

141 (base), 171, 176, 190 and 318 (M⁺)

EXAMPLE 72

To a mixture of 1.03 g of N-methyl-1-naphthylmethylamine, 0.7 g ofsodium carbonate and 10 ml of dimethylformamide was added 1.3 g of4-tert-pentylbenzyl chloride and was stirred at room temperature for 16hours. The reaction mixture was poured into water and extracted withbenzene, and the benzene solution was washed with water. Afterdistilling away benzene, 1.5 ml of concentrated hydrochloric acid wasadded and then an excess of concentrated hydrochloric acid was removed.A small amount of acetone was added and 1.33 g of formed white crystalwas filtrated. White crystal ofN-(4-tert-pentylbenzyl)-N-methyl-1-naphthylmethylamine hydrochloride(Compound of Example 12) was obtained by recrystallization from acetone.

Melting point: 191° to 193° C.

Nuclear magnetic resonance spectrum δ:

8.3 to 7.3 (m, 11H), 3.88 (s, 2H), 3.54 (s, 2H),

2.17 (s, 3H), 1.61 (q, J=7.3HZ, 2H), 1.26 (s, 6H)

0.67 (t, J=7.3HZ, 3H)

Mass spectrum (m/e):

331 (M³⁰), 190, 170, 155 and 141 (base).

EXAMPLE 73

A mixture of 3.43 g of N-methyl-naphthylmethylamine, 3.65 g of4-tert-butylbenzyl chloride, 2.33 g of anhydrous sodium carbonate and 20ml of dimethyl formamide was stirred at 50° C. for 16 hours. Thereaction mixture was poured into water and extracted with benzene, andthe benzene solution was washed with water. After distilling awaybenzene, 3 ml of concentrated hydrochloric acid was added at cooling. Anexcess of hydrochloric acid was removed under reduced pressure and asuitable amount of acetone was added. White crystal (5.9 g) wasprecipitated and was filtered.N-(4-tertbutylbenzyl)-N-methyl-1-naphthylmethylamine hydrochloride ofwhite plate crystal (Compound of Example 1) was obtained byrecrystallization from acetone/ethanol.

Melting point: 210° to 212° C.

The procedures of Example 73 were repeated to give hydrochlorides ofamine derivatives of Examples 1 to 71.

EXAMPLE 74

N-(4-Fluoro-1-naphthylmethyl)-N-methyl-4-tertbutylbenzamide (1.94 g)(Compound of Example 4) was obtained by the reaction of 1.14 g ofN-Methyl-4-fluoro-1-naphthylmethylamine and 1.24 g of 4-tert-Butylbenzylchloride.

EXAMPLE 75

N-4- tert-Butylbenzyl-N-methyl-1-(1-naphthyl)-ethylamine (1.61 g)(Compound of Example 9) was obtained by the reaction of 1.11 g ofN-Methyl-1-(1-naphthyl) ethylamine and 1.24 g of 4-tert-Butylbenzylchloride.

EXAMPLE 76

N-4-Isopropylbenzyl-N-methyl-1-naphthylmethylamine (1.75 g) (Compound ofExample 22) was obtained by the reaction of 1.03 g ofN-Methyl-1-naphthylmethylamine and 0.99 g of 4-tert-Butylbenzylchloride.

EXAMPLE 77

N-4- tert-Butylbenzyl-N-methyl-benzo[b]-thienylmethylamine (1.78 g)(Compound of Example 29) was obtained by the reaction of 0.98 g ofN-Methyl-3-benzo[b]thienylmethylamine and 1.24 g of 4-tert-Butylbenzylchloride.

EXAMPLE 78

To a mixture of 0.48 g of lithium aluminum hydride and 10 ml ofanhydrous diethyl ether was added dropwise a solution of 3.0 g ofN-methyl-N-(1-naphthylmethyl)-4-isopropylbenzamide in 10 ml of anhydrousdiethyl ether and the reaction mixture was refluxed for 24 hours. Atcooling, water was added dropwise to decompose an excess of lithiumaluminum hydride. The reaction mixture was further diluted with waterand extracted with diethyl ether, and the ether solution was washed withwater. After adding 1.5 ml of concentrated hydrochloric acid to theether solution, the ether was distilled away under reduced pressure. Asmall amount of acetone was added and formed white crystal (1.5 g) wasfiltrated. White plate crystal ofN-(4-isopropylbenzyl)-N-methyl-1-naphthylmethylamine hydrochloride(Compound of Example 22) was obtained by recrystallization fromaceton/ethanol.

Melting point: 195.5° to 197° C.

EXAMPLE 79

A mixture of 1.03 g of 1-naphthoic acid and 4.86 g of thionyl chloridewas stirred at 50° C. for 2 hours. An excess of thionyl chloride wasremoved under reduced pressure to give 1-naphthoyl chloride. A solutionof 1-naphthoyl chloride in 10 ml of benzene was added dropwise tomixture of 1.06 g of N-methyl-4-tert-butylbenzylamine, 2 ml of pyridineand 10 ml of dry benzene and was stirred for 5 hours. The resultant waspoured into water and extracted with benzene, and the benzene solutionwas washed successively with 3% aqueous solution of sodium bicarbonate,3% hydrochloric acid and water, and then dried over anhydrous sodiumsulfate. Oily product (1.74 g, amide) was obtained by distilling awaybenzene and was crystallized by leaving as it was.

Melting point: 106° to 108° C. (recrystallized from hexane/benzene)

A solution of 1.33 g of the above amide in 10 ml of ether was addeddropwise to a mixture of 0.38 g of lithium aluminum hydride and 40 ml ofanhydrous ether and was refluxed for 12 hours. After adding waterdropwise to decompose an excess of lithium aluminum hydride, theresultant was extracted with ether and washed with water. To the ethersolution was added 1 ml of concentrated hydrochloric acid. Solvent wasdistilled away under reduced pressure, a suitable amount of acetone wasadded and precipitated white crystal (1.3 g) was filtrated.N-(4-tert-Butylbenzyl)-N-methyl-1-naphtylmethylamine hydrochloride ofwhite plate crystal (Compound of Example 1) was obtained byrecrystallization from acetone/ethanol.

Melting point: 210° to 212 ° C.

Example 80

N-4-tert-Butylbenzyl-N-methyl-4-fluoro-1-naphthamide (Compound ofExample 4) was obtained by reactingN-4-tert-Butylbenzyl-N-methyl-4-fluoro-1-naphthamide.

EXAMPLE 81

N-Methyl-N-4-tert-pentylbenzyl-1-naphthylmethylamine (Compound ofExample 12) was obtained by reactingN-Methyl-N4-tert-pentylbenzyl-1-naphthamide.

EXAMPLE 82

N-4-tert-Butylbenzyl-N-methyl-3-benzo[b]-thionylmethylamine (Compound ofExample 29) was obtained by reactingN-4-tert-Butylbenzyl-N-methyl-3-benzo[b]-thenamide.

The procedures of Example 73 were repeated to give hydrochlorides ofamine derivatives of Examples 1 to 71.

EXAMPLE 83

To a mixture of 6.07 g of lithium aluminum hydride and 80 ml ofanhydrous diethyl ether was added dropwise a solution of 6.5 g ofN-(4-tert-butylbenzyl)-N-methyl-2-ethoxycarboxy-1-naphthamide in 20 mlof anhydrous benzene and was refluxed for 3 hours. At cooling, water wasadded dropwise to decompose an excess of lithium aluminum hydride andthe ether layer was separated. To the ether solution was added 3 ml ofconcentrated hydrochloric acid and an excess of hydrochloric acid wasremoved under reduced pressure. Then a small amount of acetone was addedand formed white crystal (2.12 g) was filtrated.

White crystal ofN-(4-tert-butylbenzyl)-N-methyl-2-hydroxy-1-naphthylmethylaminehydrochloride (Compound of Example 28) was obtained by recrystallizationfrom methanol/acetone.

Melting point: 181° to 183° C.

The procedures of Example 83 were repeated to give hydrochloride ofamine derivatives of Examples 1 to 71.

EXAMPLE 84

A mixture of 1.06 g of 4-tert-butylbenzoic acid and 4.86 g of thionylchloride was stirred for 2 hours at 50° C. An excess of thionyl chloridewas distilled away under reduced pressure to give acid chloride, whichwas suspended into 10 ml of dry benzene and the suspension was addeddropwise to a mixture of 1.03 g of N-methyl-1-naphthylmethylamine, 2 mlof pyridine and 10 ml of dry benzene. After stirring for 6 hours at roomtemperature, the reaction mixture was poured into water and extractedwith benzene, and the benzene solution was washed successively with 3%aqueous solution of sodium bicarbonate, 3% hydrochloric acid and waterand then dried over anhydrous sodium sulfate. Oily product (1.95 g,amide) was obtained by distilling away benzene.

A solution of the above amide in 20 ml of anhydrous ether was addeddropwise to a mixture of 0.57 g of lithium aluminum hydride and 40 ml ofanhydrous ether and refluxed for 12 hours.

After adding water dropwise to decompose an excess of lithium aluminumhydride, the resultant was extracted with ether and the ether solutionwas washed with water. At cooling, 2 ml of concentrated hydrochloricacid was added to the ether solution. Solvent was distilled away underreduced pressure, a suitable amount of acetone was added andprecipitated white crystal (1.9 g) was filtered.N-(4-tert-Butylbenzyl)-N-methyl-1-naphthylmethylamine hydrochloride ofwhite plate crystal (Compound of Example 1) was obtained byrecrystallization from acetone/ethanol.

Melting point: 210° to 212° C.

EXAMPLE 85

N-4-tert-Butylbenzyl-N-methyl-4-fluoro-1-naphthamide (Compound ofExample 4) was obtained by reactingN-(4-Fluoro-1-naphthylmethyl)-N-methyl-4-tert-butylbenzamide.

EXAMPLE 86

N-4-tert-Butylbenzyl-N-methyl-1-(1-naphthyl )-ethylamine (Compound ofExample 9) was obtained by reactingN-Methyl-N-1-(1-naphthyl)ethyl-4-tert-butyl-benzamide.

EXAMPLE 87

N-Methyl-N-4-tert-pentylbenzyl-1-naphthylmethylamine (Compound ofExample 12) was obtained by reactingN-Methyl-N-1-naphtylmethyl-4-tert-pentylbenzylamide.

EXAMPLE 88

N-4-Isopropylbenzyl-N-methyl-1-naphthylmethylamide (Compound of Example22) was obtained by reactingN-Methyl-N-1-naphthylmethyl-4-isopropylbenzamide.

EXAMPLE 89

N-4-tert-Butylbenzyl-N-methyl-3-benzo[b]-thienylmethylamine (Compound ofEXAMPLE 29 ) was obtained by reactingN-3-Benzo[b]thienylmethyl-4-tert-butylbenzamide.

Preparation Example 1 (liquid preparation)

To 500 ml of ethanol was added to dissolve 50 g of macrogol 400 and 10 gof N-(4-tert-butylbenzyl)-N-methyl-1-naphthylmethylamine hydrochlorideobtained in Example 1. To the solution was gradually added 400 g ofpurified water. To the resulting solution, ethanol was further added soas to become 1000 ml as a total amount.

Preparation Example 2 (ointment)

To a mixture of 400 g of white petrolatum, 180 g of cetanol, 50 g Ofsorbitan sesquioleate, 5 g of lauromacrogol and 1 g of propylparahydroxybenzoate, which was kept on a water bath at 80° C., was addedto dissolve 10 g ofN-(4-tert-butylbenzyl)-N-methyl-1-naphthylmethylamine hydrochlorideobtained in Example 1. To 353 g of purified water was added 1 g ofmethyl parahydroxybenzoate and warmed to 80° C. The obtained solutionwas gradually added to the former solution and stirred thoroughly.Heating was stopped and the mixture was further stirred with coolinguntil it congealed.

Preparation Example 3 (cream)

A mixture of 15 g of white petrolatum, 200 g of liquid paraffin, 50 g ofstearyl alcohol, 40 g of glyceryl monostearate, 145 g of propyleneglycol and 1 g of propyl parahydroxybenzoate was kept on a water bath at80° C. to dissolve and thereto 10 g ofN-(4-tert-butylbenzyl)-N-methyl-1-naphthylmethylamine hydrochlorideobtained in Example 1 was added to dissolve. To 40 g of polyoxyl 40stearate and 1 g of methyl parahydroxybenzoate was added 498 g ofpurified water and was kept at 80° C. to dissolve. The obtained solutionwas added to the former solution and was stirred thoroughly. Afterstirring, the resultant was futher stirred thoroughly while cooling withchilled water until it congealed.

Test Example 1

[In vitro antifungal activity test]

The antifungal activity of the compound of the present invention againstTrichophyton metagrophytes, Trichophyton interdigitale and Trichophytonrubrum was tested employing Sabouraud's agar medium.

Each test compound shown in Table 4 was dissolved into 1 ml of ethanoland thereto distilled water was added to adjust to the concentration of1000 μg/ml. In this way twofold dilution series was made, 1 ml of whichwas respectively taken into shale and therewith 9 ml of Sabouraud's agarmedium was mixed to form plate medium.

In this plate medium was implanted 0.005 ml of each test fungus at 2×10⁶spores/ml by the microplanter MIP-2 (Sakuma Seisakusho Co., Ltd.) andwas incubated at 27° C. for 7 days. The results were shown in Table 2 asthe minimal growth-inhibitory concentration (MIC, μg/ml).

                  TABLE 2                                                         ______________________________________                                        Test comound                                                                             Test fungus                                                        Example    (a)         (b)      (c)                                           ______________________________________                                         1         0.0125      0.006    0.003                                          2         0.2         0.1      0.1                                            3         0.1         0.05     0.025                                          4         0.025       0.006    0.006                                          5         0.1         0.1      0.025                                          6         0.2         0.2      0.05                                           7         0.78        0.39     0.39                                           8         0.1         0.05     0.025                                          9         0.025       0.025    0.003                                         10         1.56        1.56     0.39                                          12         0.0125      0.0125   0.006                                         13         25          25       12.5                                          14         12.5        6.25     6.25                                          15         0.78        3.13     0.39                                          16         3.13        1.56     1.56                                          17         1.56        1.56     1.56                                          18         0.1         0.05     0.006                                         19         0.78        0.2      0.2                                           20         6.25        6.25     3.13                                          22         0.025       0.1      0.0125                                        23         0.1         0.2      0.1                                           24         0.1         0.2      0.1                                           25         0.78        0.78     0.39                                          26         12.5        12.5     6.25                                          28         25          12.5     6.25                                          29         0.05                 0.05                                          30         0.78                 0.78                                          33         0.2                  0.1                                           34         0.025                0.025                                         35         0.78                 0.78                                          39         0.39                 0.39                                          43         0.2                  0.2                                           49         0.39                 0.39                                          51         0.39                 0.2                                           54         0.1                  0.1                                           56         0.2                  0.2                                           63         0.39                 0.1                                           69         0.05                 0.025                                         ______________________________________                                         (a) Trichophyton mentagrophytes                                               (b) Trichophyton interdigitale                                                (c) Trichophyton rubrum                                                  

As the result of Test, all test compounds shown in Table 2 were provedto have antifungal activity.

Test Example 2

[Test on treatment of trichophytosis]

In the back of male Hartley guinea pig weighing 600 to 700 g, fourportions were unhaired in an area of 4 cm² respectively and rubbedlightly with sandpaper, to which the second generation of Trichophytonmentagrophytes incubated inversely from another guinea pig was infectedat 1×10⁵ spores per portion. The test compounds obtained in Example 1was dissolved in ethanol and 0.2 ml of the resultant 0.1% solution wasapplied to the infected portions once in a day for ten days since 48hours after the infection. Test animal was killed 2 days after the lasttreatment and 10 tissue specimens from each infected portions wereplaced on Sabouraud's plates containing cycloheximide and kanamycin,which were incubated at 27° C. for 7 days. After incubation, existenceof fungi was observed and inhibitory ratio calculated according to thefollowing equation showed high value of 82%. ##EQU1##

Two portions in the back of male Hartley guinea pig weighing 600 to 700g were unhaired in an area of 4 cm² respectively in order to examineside effects of the test compounds. The next day unhaired portions werelightly rubbed with sandpaper. The test compounds obtained in Example 1was dissolved in ethanol and 0.2 ml/day of the resultant 0.5% solutionwas applied to one of the unhaired portions, while 0.2 ml/day of onlyethanol was applied to the other portions, once in a day for ten daysrespectively.

As the result of test, side effects such as, for instance, erythema andpapula were not observed.

I claim:
 1. An amine derivative represented by formula (I): ##STR100##wherein X is selected from the group consisting of: ##STR101## and Y isselected from the group consisting of ##STR102## and ##STR103## providedthat Y cannot be ##STR104## when X is ##STR105## and further providedthat Y cannot be ##STR106## when X is ##STR107## R¹ is hydrogen atom oran alkyl group of 1 to 6 carbon atoms or a halogenated alkyl group;R² ishydrogen atom or an alkyl group of 1 to 6 carbon atoms; R³ is hydrogenatom or an alkyl group of 1 to 6 carbon atoms; R⁴ is hydrogen atom, analkyl group of 1 to 10 carbon atoms, a cycloalkyl group of 3 to 7 carbonatoms or a halogenated alkyl group; R⁵ is hydrogen atom, an alkyl groupof 1 to 6 carbon atoms, a halogen atom or a nitro group, wherein R⁵ isattached to an arbitrary position of X, and R³ or R⁴ is attached to anarbitrary position of Y.
 2. A fungicide composition containing an aminederivative represented by formula (I): ##STR108## wherein X is selectedfrom the group consisting of ##STR109## and Y is selected from the groupconsisting of ##STR110## and ##STR111## provided that Y cannot be##STR112## when X is ##STR113## and further provided that Y cannot be##STR114## when X is ##STR115## R¹ is hydrogen atom or an alkyl group or1 to 6 carbon atoms or a halogenated alkyl group;R² is hydrogen atom oran alkyl group of 1 to 6 carbon atoms; R³ is hydrogen atom or an alkylgroup of 1 to 6 carbon atoms; R⁴ is hydrogen atom, an alkyl group of 1to 10 carbon atoms, a cycloalkyl group of 3 to 7 carbon atoms or ahalogenated alkyl group; R⁵ is hydrogen atom, an alkyl group of 1 to 6carbon atoms, halogen atom or a nitro group, wherein R⁵ is attached toan arbitrary position of X, and R³ or R⁴ is attached to an arbitraryposition of Y.